chr12-122232318-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP6_Moderate
The NM_022916.6(VPS33A):c.1719A>G(p.Glu573=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,614,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
VPS33A
NM_022916.6 synonymous
NM_022916.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.297
Genes affected
VPS33A (HGNC:18179): (VPS33A core subunit of CORVET and HOPS complexes) This gene encodes a tethering protein and a core subunit of the homotypic fusion and protein sorting (HOPS) complex. The HOPS complex and a second endosomal tethering complex called the class C core vacuole/endosome tethering (CORVET) complex, perform diverse functions in endocytosis including membrane tethering, RabGTPase interaction, activation and proofreading of synaptic-soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) assembly to drive membrane fusion, and endosome-to-cytoskeleton attachment. The HOPS complex controls endosome maturation as well as endosome traffic to the lysosome. This complex is essential for vacuolar fusion and is required for adaptor protein complex 3-dependent transport from the golgi to the vacuole. The encoded protein belongs to the Sec1/Munc18 (SM) family of SNARE-mediated membrane fusion regulators. Naturally occurring mutations in this gene are associated with a novel mucopolysaccharidosis-like disease. [provided by RefSeq, Apr 2017]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP6
?
Variant 12-122232318-T-C is Benign according to our data. Variant chr12-122232318-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2414850.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
VPS33A | NM_022916.6 | c.1719A>G | p.Glu573= | synonymous_variant | 13/13 | ENST00000267199.9 | |
VPS33A | NM_001351018.2 | c.1686A>G | p.Glu562= | synonymous_variant | 13/13 | ||
VPS33A | NM_001351019.2 | c.1671A>G | p.Glu557= | synonymous_variant | 13/13 | ||
VPS33A | NM_001351020.2 | c.1398A>G | p.Glu466= | synonymous_variant | 11/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
VPS33A | ENST00000267199.9 | c.1719A>G | p.Glu573= | synonymous_variant | 13/13 | 1 | NM_022916.6 | P1 | |
VPS33A | ENST00000643696.1 | c.1842A>G | p.Glu614= | synonymous_variant | 14/14 | ||||
VPS33A | ENST00000543633.5 | c.*1680A>G | 3_prime_UTR_variant, NMD_transcript_variant | 14/14 | 5 | ||||
VPS33A | ENST00000544349.6 | c.*1698A>G | 3_prime_UTR_variant, NMD_transcript_variant | 14/14 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152196Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251442Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135900
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GnomAD4 exome AF: 0.0000144 AC: 21AN: 1461888Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11AN XY: 727244
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Apr 20, 2023 | - - |
Computational scores
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Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: 1
Find out detailed SpliceAI scores and Pangolin per-transcript scores at